Biogenic amino O- and N-methyltransferases involving S-adenosylmethionine will be purified and characterized to determine their physiological roles in the biosynthesis and inactivation of catecholamine neurotransmitters and hormones, and to assess their possible implication in the formation of endogenous hallucinogenic O-and N-methyl derivatives of neurotransmitters. The specific enzymes are catechol-O-methyltransferase (COMT), indoleamine-N-methyltransferase (INMT), histamine-N-methyltransferase (HNMT), hydroxyindole-O-methyltransferase (HIOMT), phenethanolamine-N-methyltransferase (PNMT), iodophenol-O-methyltransferase (IPOMT), 3,4-dimethoxyphenylethylamine (DMPEA) and mescaline forming enzymes. Among these, catechol-O-methyltransferase (COMT), which has been shown by us to exist in rat and human livers as multiple molecular forms, designated as I & II, which differ in size and charge, will be further characterized, with an emphasis on the elucidation of molecular basis of enzyme multiplicity. A new purification procedure for the two distinct forms of COMT from rat and human livers has been devised. A simple affinity chromatography procedure as well as a rapid chromatographic method for determination of the two forms of COMT in a large number of animal samples is being developed. Other biogenic amino methyltransferases, which show marked tissue- as well as species-specific distribution of enzyme activity and some of which exhibit molecular heterogeneity within a species, will be purified from various organs of several mammalian species and further characterized to define their properties substrate specificity, physicochemical, molecular, catalytic and kinetic properties.